Behavioral/Systems/Cognitive

The analgesic potency of opiates varies greatly among individuals, and is influenced by many factors, including genotype, sex, and source of pain. Morphine is typically more potent in male laboratory animals than in females, but the opposite might be true in humans. Loyd et al. hypothesized that differences in μ-opioid receptor (MOR) expression underlie sex differences in morphine potency. They found that male rats had greater MOR expression in the caudal ventrolateral periaqueductal gray (PAG) than females. Moreover, morphine injections into the PAG reversed inflammatory thermal hyperalgesia in males, but were significantly less potent in female rats. Finally, selective elimination of MOR-expressing neurons in the PAG reduced the analgesic potency of systemic morphine treatment in male rats, but not in females. Although these results might not have direct implications for sex differences in morphine potency in humans, they suggest that differences in receptor expression contribute to individual variability in morphine sensitivity.

Thyroid hormones are essential regulators of nervous system development, promoting not only axonal and dendritic growth, but also differentiation and maturation of myelinating oligodendrocytes. Harsan et al. reasoned that these effects could be reproduced in adult animals treated with thyroid hormone, providing a potential treatment for demyelinating diseases such as multiple sclerosis. The authors fed mice cuprizone, a gliotoxic copper chelator, and evaluated myelin integrity in vivo using diffusion tensor magnetic resonance imaging (DT-MRI). Cuprizone treatment caused severe demyelination in the corpus callosum and cerebellum that persisted after cuprizone withdrawal. Subsequent triiodothyronine (T3) hormone treatment led to complete recovery of myelination. Immunohistochemical analysis suggested that T3 increased the generation of oligodendrocyte precursor cells, as well as their migration, differentiation, maturation, and remyelination of axons. Importantly, remyelination processes continued after T3 treatment was terminated, suggesting that prolonged thyroid hormone elevation (and its undesirable side effects) might not be required to produce beneficial effects.